Antimicrobial peptides (AMPs) are ubiquitous in nature and play an important role in the innate immune system of many species (Zasloff, M., Nature (2002) 415:389-395; Epand, R. M., and Vogel, H. J., Biochim Biophys Acta (1999) 1462:11-28). Antimicrobial peptides are diverse in structure, function, and specificity. The biological activity of antimicrobial peptides ranges from broad spectrum (active against both Gram positive and Gram negatives) and non-hemolytic (e.g., magainin) to broad spectrum and highly hemolytic (e.g., melittin). For commercial applications of AMPs, it is desirable to increase the bactericidal activity and decrease the hemolytic activity.
One major class of antimicrobial peptides consists of linear α-helical peptides, such as cecropin and magainin. Haynie (U.S. Pat. No. 5,847,047) described synthetic peptides based on a heptad repeat and comprised of Leu and Lys residues that were designed to adopt an α-helical amphiphilic structure. These peptides exhibited activity at 8-63 μg/mL against Escherichia coli and Staphylococcus aureus in solution, however they also exhibited moderate hemolytic activity.